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Abstract
A comprehensive understanding of Dirofilaria immitis, canine heartworm, requiresthorough investigation into each life stage to understand not only the mechanisms of parasite
establishment within the host, but also host-parasite interaction during establishment. Due to the
limited availability of D. immitis in research settings, the majority of in vitro studies focus on the
microfilariae and third-stage larval life stages of the parasite. Current in vivo D. immitis research
relies on an established infection in a permissive host, and the best animal models for these
studies are dogs and ferrets. Rodent animal models are generally preferred by researchers for in
vivo work due to the nature of the research and economics; however, previous studies have
attempted to establish infection in immunocompetent mice, rats, and jirds without success. The
studies in this dissertation are innovative for three reasons: Chapter 2 describes the first study to
characterize the initial cellular immune response of a nonpermissive host, the Mongolian gerbil,
to D. immitis intraperitoneal infection. Chapter 3 describes the first study to explore the role of
gerbil peritoneal exudate cells with flow cytometry and is the first to deplete gerbil peritoneal
macrophages. Chapter 4 describes differential splicing of SLO-1 that could underlie differences
in emodepside activity against relevant D. immitis life stages. In the studies of this dissertation,
we hypothesized that the establishment of D. immitis in the definitive host is determined by that
host's immune response to the presence of larvae. The results of these proposed studies will fill
in a gap of knowledge regarding the determinants of filarial host specificity. The results also
provide insight into the anti-filarial mechanisms of the host, which may be used to discover a
preventive and/or therapeutic in the future. Not only will the results of these studies impact the
field of canine heartworm research, but they can also lead to more targeted eradication efforts of
other types of human and animal infectious filarial diseases.